The main purpose of this investigation continues to be the definition of the extent of autonomy of the mitochondrion in its biogenesis. During the grant period our aim will be 1) A more extended identification and complete documentation of the polypetides sythesized by the mitochondria and a test of their function, whether participating in the catalytic process or integration into the mitochondrial membrane. 2) The development of methods for the dissociation of mitochondrial enzyme complexes into their mitochondrially and cytoplasmically synthesized subunits; the characterization of these partially or completely resolved enzymes and their reconstitution, including models for their interaction with other enzyme complexes and the mitochondrial membrane. 3) An investigation into the genetic capabilities of wild type Rho positive and mutant Rho negative mitochondrial DNAs, their interconversion by representatives of three classes of mutagens (ethidium bromide, berenil, euflavine) and modulating agents such as Antimycin A. Special emphasis will be placed on documenting the possible involvement of various components of the mitochondrial damage repair system and the inner membrane. Coincident with these studies we will investigate the function and interaction of these mitochondria with other entities in the nucleus and cell sap during cellular activity, proliferation and differentiation, as well as the regulation of these processes. BIBLIOGRAPHIC REFERENCES: H.R. Mahler. Integration and Regulation of Mitochondrial Assembly in Yeast. Molecular and Cellular Biochemistry, in press (1976). S.H. Phan and H.R. Mahler. Studies on Cytochrome Oxidase. IV. Partial Resolution of Enzymes Containing Seven or Six Subunits, from Yeast and Beef Heart, Respectively. J. Biol. Chem., in press (1976).